Is BEND4 p.Phe62Leu (c.186C>G) pathogenic?

BEND4 p.Phe62Leu (c.186C>G) is classified Uncertain significance in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: likely pathogenic (0.7777); Very rare (popmax 0.00473%, nfe).

How common is BEND4 p.Phe62Leu (c.186C>G) in the general population?

BEND4 p.Phe62Leu (c.186C>G) is very rare (popmax 0.00473%, nfe) (gnomAD).

What do computational predictors say about BEND4 p.Phe62Leu (c.186C>G)?

AlphaMissense predicts likely pathogenic (score 0.7777) — an in-silico prediction, not a clinical call.

BEND4 p.Phe62Leu

c.186C>G · rs1375938460 · VCV2483122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00473%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7777	likely pathogenic
REVEL	0.096	moderately benign-leaning
SaProt	LLR -3.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.79, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	18.62	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00473% European (non-Finnish) · 47/992,896 alleles

Filtering AF 0.00365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00327%

Overall 0.00393% 49/1,248,382 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00473%	21,125
Remaining individualsnot grpmax-eligible	0.00436%	22,922

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BEND4
Protein: p.Phe62Leu
Coding: c.186C>G
MANE Select: NM_207406
dbSNP: rs1375938460
Type: single nucleotide variant
Location: chr4:42151958 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57
Residue 62: the 'disordered' region

Full BEND4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND4 p.Phe62Val Uncertain significance ★ ⚠ same residue
BEND4 p.Gln224Glu Uncertain significance ★★ ⚠ same type
BEND4 p.Ser268Leu Uncertain significance ★★ ⚠ same type
BEND4 p.Pro473= Likely benign ★★ same type
BEND4 p.Ala125Thr Uncertain significance ★ ⚠ same type
BEND4 p.Ala244Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala518Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala66Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bend4-p-phe62leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown